Oxygen toxicity: unique cytoprotective properties of vitamin E succinate in hepatocytes.
Freshly isolated rat hepatocytes suspensions were incubated under an atmosphere of 95% O2/5% CO2 or 95% air/5% CO2 for 10 h. Cell injury and death were observed between the 6th and 10th hour of incubation, only in 95% O2-treated hepatocytes. Oxygen-induced injury was preceded by marked lipid peroxidation and rapid depletion of cellular alpha tocopherol content. The exogenous administration of unesterified alpha tocopherol (T, 25 microM) resulted in a 20-fold increase in cellular T levels (4.2 nmol/10(6) cells) but failed to protect these hepatocytes from the toxic effects of oxygen. In contrast, hepatocytes incubated with 25 microM of the succinate ester of alpha tocopherol (TS) contained both TS (3.0 nmol/10(6) cells) and T (1.4 nmol/10(6) cells) and were completely protected from the toxic effects of oxygen, including the induction of lipid peroxidation. These findings suggest that TS cytoprotection results not from the cellular accumulation of T but rather, from cellular TS accumulation. The data also indicate that the depletion of cellular T is not the critical cellular event that is responsible for hyperoxia (reactive oxygen intermediate)-induced injury. Instead, it appears that TS possesses unique cytoprotective properties that intervene in the critical cellular events that lead to oxygen toxicity. Thus, vitamin E succinate and our hyperoxic hepatocyte preparation provide a promising new model system for the study and prevention of tissue damage resulting from the toxic effects of hyperoxia and reactive oxygen intermediates.
Fariss
M W
MW
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0662.
D000818:Animals; D002470:Cell Survival; D005609:Free Radicals; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D005609:Free Radicals; D014810:Vitamin E; D024505:Tocopherols; D010100:Oxygen